A Phase 2 Clinical Trial Exploring 3-Dimensional Imaging of Androgen Deprivation Induced Osteoporosis, Radiotherapy Hypofractionation and the Prognostic Significance of Micrometastatic Disease in Men With Prostate Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Prediction of ADT induced bone mineral density loss
研究概览
简要总结
This is a single centre prospective observational noninterventional study of men with histological confirmed prostate cancer, high risk disease and not positive for metastatic disease planned to receive Radiotherapy and 18 months of Androgen Deprivation Therapy (ADT). Although ADT improves the chance of cure, it can also have many side effects. One of these is bone mineral density loss. When this is advanced, it is called osteoporosis. Men with osteoporosis have a higher chance of getting fractures of bones such as the hip and spine. Currently, the best way to measure for osteoporosis is to do a bone mineral density scan using a DEXA scanner.
The primary objective of this study is to see if baseline Magnetic Resonance Imager (MRI) and a Computer Tomogram (CT) combined with clinical factors predicts which men are at greater risk of accelerated ADT induced bone mineral density loss than baseline DEXA scanning alone. The data from the patients will be used to construct a model predicting annual rate of bone loss based on baseline imaging, clinical and biochemical characteristics.
Secondary aims for this study are as follows:
- Evaluating the feasibility, toxicity (acute and late) and efficacy (5 year biochemical control by the Phoenix definition)of multimodality therapy with hypofractionated radiotherapy (giving a larger dose of radiotherapy over a shorter time 5½ weeks compared with a standard 8 week approach). Although used overseas, this 5½ week regimen has not been used widely in Australia, and we would like to see if we gain similar results here as have been reported from the US.
- Feasibility and efficacy of a risk adapted duration of neoadjuvant hormonal therapy. Usually, ADT is given for between 19 months before radiotherapy is started but there is no agreement as to which duration is best. This trial aims to tailor the duration of ADT prior to radiotherapy based on blood PSA test results.
- Prognostic value of circulating tumour cells (CTCs). This is a blood test which can detect cancer cells in the blood which has been used for patients with metastatic cancer. The presence of CTCs in men with prostate cancer correlated with poorer overall survival. Potentially, high risk prostate cancer patients with CTCs detected may represent a very high risk group and could therefore warrant treatment intensification.
- To correlate bone marrow changes on MRI with changes in blood counts and patient reported fatigue. Measuring bone marrow may help in predicting not just which patients are at risk of losing bone faster but also of becoming anaemic, and suffering fatigue. A correlation may better explain some of the toxicities associated with ADT.
- Implementation of a nomogram based radiotherapy target delineation algorithm. This trial aims to use a decision making tool called a nomogram to help tailor the area to treat in a more standard way.
详细描述
- ADT induced Osteoporosis
Prostate cancer is a common malignancy in Australian men. In men with localized disease at the time of diagnosis, baseline PSA level, tumour stage and Gleason grade can be used to help stratify into risk categories. Men with high risk disease are defined by an absence of metastatic disease using conventional imaging, and any one of the following: a presenting PSA of >20, Gleason grade 8-10 disease on histology, or stage T3-4 disease.[1] Such men are often treated with a combination of radiotherapy to the prostate and pelvic lymph nodes, in conjunction with a course of adjuvant androgen deprivation therapy (ADT) of between 18-36 months.[2] Recent literature suggests that the greatest benefit from adjuvant ADT comes from the first 4-6 months of treatment, and although there is measurable benefit from prolonging the course of ADT, it follows the law of diminishing returns with progressively smaller benefit per unit of increased treatment time.[3] This is important, in that if cumulative toxicities are being inflicted by prolonging the treatment, there is likely to be a duration where the harm of further treatment will start to outweigh the shrinking disease control benefits.
With greater clinical experience of the use of adjuvant ADT, there has become a better awareness of the toxicities associated with this treatment. Accelerated loss of bone mineral density has long been recognized as a complication of being hypogonadal. There is now good evidence that this leads to an approximately 7% higher risk of fractures for men with prostate cancer managed with ADT.[4] Osteoporotic fractures are associated with increased morbidity and mortality, and a high proportion of patients who suffer them never fully regain their pre-fracture level of functioning.
There are Australian guidelines for the management of osteopaenia / osteoporosis for men managed with ADT.[5, 6] They recommend monitoring of bone mineral density (BMD) using annual DEXA scanning, supplementary Vitamin D with Calcium, and the use of bisphosphonate therapy for men with prevalent minimal trauma fracture or baseline BMD T-Score <-2.0. One point high-lighted is that there is a wide spectrum in the rate of bone mineral loss between patients and techniques of measurement, with figures as high as 8% per year reported. This is far in excess of a normal rate of bone loss amongst males of 0.5% per year.[7]
Although validated nomograms exist for the general population combining DEXA findings with clinical parameters to predict long term fracture risks, no such tool exists for men rendered hypogonadal with the use of ADT.[8] Guidelines for men on ADT are empirical, and largely copy risk factors from the general population.[9]
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Prediction of ADT induced bone mineral density loss
时间窗: 6 years
That baseline MR and CT imaging of lumbar spine cortical bone, trabecular bone, marrow and fat fraction combined with clinical factors predicts which men are at greater risk of accelerated Androgen Deprivation Therapy (ADT) induced bone mineral density loss than baseline DEXA scanning alone.
次要结局
- Feasibility, toxicity and efficacy of multimodality therapy with hypofractionated radiotherapy(5 years)
- To correlate marrow changes on MR with changes in blood counts and patient reported fatigue(6 years)
- Prognostic value of circulating tumour cells(6 years)
- Implementation of a risk adapted duration of neoadjuvant hormonal therapy(6 years)
- Implementation of a nomogram based radiotherapy target delineation algorithm(6 years)
研究者
Dr Jarad Martin
Associate Professor Jarad Martin
Calvary Mater Newcastle, Australia